FDA approves drug to treat nerve disease based on discoveries made at UMass Medical School

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The U.S. Food and Drug Administration has approved patisiran, a novel RNAi therapeutic for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients. Developed by Cambridge biotech company Alnylam, patisiran is the first FDA-approved therapeutic using RNA interference, a natural cellular process of gene silencing that was first described in a 1998 paper in Natureby UMass Medical School researcher Craig Mello, PhD, and Stanford professor Andrew Fire, PhD.

Dr. Mello and Dr. Fire's work was recognized with the 2006 Nobel Prize in Physiology or Medicine and heralded a new era of scientific discovery and drug development. RNA interference works by harnessing a natural process of gene regulation to turn off the expression of a damaged or misfiring gene, which can be the basis for numerous diseases.

After the Nature paper, a series of seminal advances of the science followed rapidly, including work by UMMS professor Phillip D. Zamore, PhD, who in 2000 was lead author on a landmark paper in Cell that proved double-stranded RNA is chopped up into small interfering RNAs—the specific determinant for RNAi. Two years later, Dr. Zamore, along with three collaborators, formed Alnylam Pharmaceuticals to explore RNAi-based drug development.

"Twelve years after being awarded the Nobel Prize with Andrew Fire for our description of RNA interference, seeing the first RNAi therapeutic approved to treat patients is one of my proudest moments," said Mello, Howard Hughes Medical Institute Investigator, the Blais University Chair in Molecular Medicine and distinguished professor of RNA therapeutics and molecular medicine.

"To see our fundamental work make the journey from the lab to the clinic has been one of the most rewarding adventures of my life," said Dr. Zamore, Howard Hughes Medical Institute Investigator, the Gretchen Stone Cook Chair of Biomedical Sciences and chair and professor of RNA therapeutics. "I can now proudly tell my kids that sick people are getting better because the American taxpayer supported fruit fly research in places like Worcester, Massachusetts!"

Patisiran, which will be commercialized under the name Onpattro, had previously been granted Fast Track Designation, Breakthrough Therapy Designation and an expanded Orphan Drug Designation by the FDA. The drug has already been given initial approval by the European Medicines Agency, which approves new drugs for the European Community.

"This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR," said FDA Commissioner Scott Gottlieb, MD, in the announcement. "It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.

"This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms. New technologies like RNA inhibitors, that alter the genetic drivers of a disease, have the potential to transform medicine, so we can better confront and even cure debilitating illnesses. We're committed to advancing scientific principles that enable the efficient development and review of safe, effective and groundbreaking treatments that have the potential to change patients’ lives."

Earlier this year, Alnylam reported in the New England Journal of Medicine that patisiran improved measures of quality of life, activities of daily living, ambulation, nutritional status and autonomic symptoms relative to placebo in patients with hATTR amyloidosis, an inevitably progressive and generally fatal disease. Patisiran treatment also led to favorable effects on exploratory endpoints related to cardiac structure and function in patients with cardiac involvement.

One of the challenges facing the development of therapeutics that use the power of RNAi has been delivering the short interfering RNA strands that silence a gene’s activity. Alnylam's patisiran is the first drug to market where that problem has been solved.